Don S. Dizon, MD, on Ovarian and Other Extrarenal Clear Cell Carcinomas: Update on Nivolumab and Ipilimumab

I will be presenting BrUOG 354 which is a two-arm randomized non-comparative clinical trial that enrolled people with extrarenal clear cell carcinoma. And tested two regimens, both of them immunotherapeutic. One used nivolumab alone, and the other used nivolumab plus ipilimumab. We enrolled 46 people to this trial, 44 of whom were treated. All of these patients had a diagnosis of clear cell cancers of the gynecological tract. And that's important because clear cell cancers when you compare them to the more common serous type cancers, are associated with a worse prognosis. They do not respond as well to our standard chemotherapies, are prone to relapse more frequently. And unfortunately in the context of recurrent disease, they do not respond as well to treatment. So the prognosis is actually quite poor. This prompted this clinical trial. And it was actually based on some very preliminary data where people were seeing clinical complete responses in folks with clear cell cancers. To this point, before this trial was presented, there had been two trials of immunotherapy in ovarian cancer. One suggesting that clear cell cancer was associated with a five-fold higher response rate compared to other histologies. Although that clinical trial which was done by NRG Oncology group, only enrolled 12 people with clear cell. For that, suggestion was made. And the other was a SWOG clinical trial that enrolled 18 people with ovarian cancer and showing that the combination of nivolumab and ipilimumab was effective with some durability, again, based on a very small number of patients. So our trial which enrolled 46 people, is the largest trial in this very rare cancer population. What we can report is that both single-agent nivolumab, and nivolumab and ipilimumab have activity in clear cell cancers, and both are associated with survival outcomes although the one with combination therapy is longer. The overall response rate with single-agent nivolumab is 13%, which includes two partial responses. Median progression free survival is two months, and median overall survival in this trial was less than six months. With the combination therapy, the overall response rate was 33% with five complete responders. Median progression free survival in that arm was 17 months, and median overall survival is 24 months. And importantly for those who responded to the combination, the response was durable. And we had several patients who remain on study past two years, including up to today.